Systemic lupus erythematosus (SLE) is an autoimmune disease which is caused by the ‘self-attack’ by the immune system against the body and results in inflammation and tissue damage1. It has a strong predilection in women with a female to male ratio of around 9:1 and peak onset during child-bearing years2. It can manifest in a chronic manner or be of a form that has recurrent relapses. Unlike other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, SLE is considered to be a prototypic systemic autoimmune disease3,4. It has the potential of affecting multiple organ systems including the skin, muscles, bones, lungs, kidneys, cardiovascular and central nervous systems. Renal complications, infections, myocardial infarction and central nervous system involvement are the major causes of morbidity and even death in SLE patients5. The 10-year survival rate is about 70%6. The extremely diverse and variable clinical manifestations present a challenge on the SLE management to clinicians.
SLE is characterized by the loss of immunologic self-tolerance and production of autoantibodies. Serum anti-double-stranded (ds) DNA antibody titer of SLE patients is used as a serologic means to assess the disease activity. However, about 30% SLE patients are negative for this test even during the active stage. On the other hand, positive anti-ds DNA antibody has been reported in patients with other diseases, such as rheumatoid arthritis and certain dermatologic disorders7,8.
The etiology of SLE remains enigmatic9; however cell death has been regarded as an important event in the pathogenesis of SLE as it leads to the release of antigens, such as nucleic acids, for immune complex formation which may trigger a cascade of immune responses against the body of the SLE patients10-14. In fact, defects in the mechanism of cell death including accelerated apoptosis of lymphocytes and macrophages15,16, impairment in the clearance of dead cells17 and deficiency in DNase activity18,19 have been implicated in SLE and suggested to result in the generation of extra-cellular auto-antigens11-14.
SLE was one of the pathological conditions reported to be associated with the presence of circulating DNA20. Since then, studies using various methods have consistently demonstrated elevations of circulating DNA in SLE patients21-23. In addition, some early reports have highlighted that the circulating DNA that form immune complexes with auto-antibodies in SLE patients display a characteristic fragmentation pattern which resembles the DNA laddering pattern of apoptosis by gel electrophoresis24-26. These findings have implicated the association between the pathogenesis of SLE, apoptosis and circulating nucleic acids. However, further studies on the biological and pathophysiological characteristics of circulating nucleic acids in SLE were few.